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Oxidation — aryl C–C to C–O migration

Dakin oxidation

How the Dakin oxidation works, in 3 steps. Each step shows the structures and the curved arrows that move the electrons.

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In short. A 3-step mechanism. Typical reagents: H₂O₂, NaOH (aq.). Conditions: Aqueous base, 0–25 °C. Bonds formed: C–O (aryl–O); formate; bonds broken: aryl C–C(=O); O–O. Stereochemistry: None (aromatic); aryl migrates with retention of its ring. Rate and selectivity: Migration of the electron-rich aryl is rate-limiting.

At a glance

ReagentsH₂O₂, NaOH (aq.)
Solvent / conditionsAqueous base, 0–25 °C
Bonds formedC–O (aryl–O); formate
Bonds brokenaryl C–C(=O); O–O
StereochemistryNone (aromatic); aryl migrates with retention of its ring
Rate / selectivityMigration of the electron-rich aryl is rate-limiting

Step 1: HOO⁻ adds to the aldehyde

+OOHOOHOOOHOH1 · HOO⁻ ADDS TO THE ALDEHYDEhydroperoxide anionHO₂⁻NUCLEOPHILE4-hydroxybenzaldehydeC₇H₆O₂ELECTROPHILEperoxy-alkoxideC₇H₇O₄⁻INTERMEDIATE

Hydroperoxide anion (from H₂O₂ and base) attacks the carbonyl of an ortho- or para-hydroxy benzaldehyde, forming a tetrahedral peroxy-alkoxide. The free phenol OH or O⁻ on the ring is what makes this work, because it pushes electron density into the ring during the next step.

Step 2: Aryl shift, O–O cleavage

1,2-aryl shift+OOOHOHOOOHOH2 · ARYL SHIFT, O–O CLEAVAGEperoxy-alkoxideC₇H₇O₄⁻INTERMEDIATEaryl formateC₇H₆O₃INTERMEDIATEhydroxideHO⁻LEAVING GROUPLike Baeyer–Villiger: the electron-rich aryl migrates; the para-OH (or O⁻) pushes density in.

The aryl group migrates from carbon to oxygen as the O–O bond breaks and hydroxide leaves — the same Baeyer-Villiger-type 1,2-shift, with the electron-rich aryl ring the best migrating group. This gives an aryl formate ester.

Step 3: Hydrolysis: hydroquinone + formate

++OHOOOHOOHOOHOOHOOHOHOHOO3 · HYDROLYSIS: HYDROQUINONE + FORMATEhydroxideHO⁻NUCLEOPHILEaryl formateC₇H₆O₃ELECTROPHILEtetrahedral intermediateC₇H₇O₄⁻INTERMEDIATEtetrahedral intermediateINTERMEDIATEhydroquinoneC₆H₆O₂PRODUCTformateCHO₂⁻BYPRODUCTThe aldehyde carbon leaves as formate; the ring now carries an OH.

Hydroxide hydrolyzes the formate ester, releasing formate and a catechol (ortho case) or hydroquinone (para case). The net result is that the aldehyde carbon is excised and replaced by an OH on the ring.

Abbreviations and terms

NaOH
Sodium hydroxide. Strong aqueous base and nucleophile.
H2O2
Hydrogen peroxide. Oxidant; its anion HOO⁻ is an excellent nucleophile.

How it compares with related reactions

Dakin oxidationBaeyer-Villiger oxidation of a ketoneSwern oxidation of a primary alcohol
ReagentsH₂O₂, NaOH (aq.)mCPBA or CH₃CO₃H (peracid)DMSO, (COCl)₂, then Et₃N
ConditionsAqueous base, 0–25 °CCH₂Cl₂, 25 °C; cat. acid helpsCH₂Cl₂, –78 °C then warm to 25 °C
StereochemistryNone (aromatic); aryl migrates with retention of its ringRetention at the migrating carbonRetains α-stereocentres (no epimerization)
Rate / selectivityMigration of the electron-rich aryl is rate-limitingMigratory aptitude: tert > cyclohexyl ≈ sec > Ph > prim > MeActivation at –78 °C; ylide collapse fast on warming

Test yourself

Try to answer each question before opening it.

Which reagents and conditions are typical for the Dakin oxidation?

H₂O₂, NaOH (aq.). Conditions: Aqueous base, 0–25 °C.

Which bonds are formed and which are broken?

Formed: C–O (aryl–O); formate. Broken: aryl C–C(=O); O–O.

What is the stereochemical outcome?

None (aromatic); aryl migrates with retention of its ring

What controls the rate or the selectivity?

Migration of the electron-rich aryl is rate-limiting

Study guides that help with this reaction

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